The present invention relates generally to methods for imaging objects located in turbid media and more particularly to a novel method for imaging objects located in turbid media.
As can readily be appreciated, there are many situations in which the detection of an object present in a turbid, i.e., highly scattering, medium is highly desirable. For instance, the detection of a tumor embedded within a tissue is one such example. Although X-ray techniques do provide some measure of success in detecting objects in turbid media, they are not typically well-suited for detecting very small objects, e.g., tumors less than 1 mm in size embedded in tissues, or for detecting objects in thick media. In addition, X-ray radiation can present safety hazards to a person exposed thereto. Ultrasound and magnetic resonance imaging (MRI) offer alternatives to the use of X-rays but have their own drawbacks.
Another technique used to detect objects in turbid media, such as tumors in tissues, is transillumination. In transillumination, visible light is incident on one side of a medium and the light emergent from the opposite side of the medium is used to form an image. Objects embedded in the medium typically absorb the incident light and appear in the image as shadows. Unfortunately, the usefulness of transillumination as a detection technique is severely limited in those instances in which the medium is thick or the object is very small. This is because light scattering within the medium contributes to noise and reduces the intensity of the unscattered light used to form the image shadow.
To improve the detectability of small objects located in a turbid medium using transillumination, many investigators have attempted to selectively use only certain components of the transilluminating light signal. This may be done by exploiting the properties of photon migration through a scattering medium. Photons migrating through a turbid medium have traditionally been categorized into three major signal components: (1) the ballistic (coherent) photons which arrive first by traveling over the shortest, most direct path; (2) the snake (quasi-coherent) photons which arrive within the first .delta.t after the ballistic photons and which deviate, only to a very slight extent, off a straight-line propagation path; and (3) the diffusive (incoherent) photons which experience comparatively more scattering than do ballistic and snake photons and, therefore, deviate more considerably from the straight-line propagation path followed by ballistic and snake photons.
Because it has been believed that ballistic and snake photons contain the least distorted image information and that diffusive photons lose most of the image information, efforts to make transillumination work most effectively with turbid media have traditionally focused on techniques which involve the preferential detection of ballistic and snake photons over diffusive photons. The preferential selection of ballistic and snake photons over diffusive photons has traditionally been implemented by using various time-gating, space-gating and time/space-gating techniques. Patents and publications which disclose certain of these techniques include U.S. Pat. No. 5,140,463, inventors Yoo et al., which issued Aug. 18, 1992; U.S. Pat. No. 5,143,372, inventors Alfano et al., which issued Aug. 25, 1992; U.S. Pat. No. 5,227,912, inventors Ho et al., which issued Jul. 13, 1993; U.S. Pat. No. 5,371,368, inventors Alfano et al., which issued Dec. 6, 1994; Alfano et al., "Photons for prompt tumor detection," Physics World, pp. 37-40 (January 1992); Wang et al., "Ballistic 2-D Imaging Through Scattering Walls Using an Ultrafast Optical Kerr Gate," Science, Vol. 253, pp. 769-771 (Aug. 16, 1991); Wang et al., "Kerr-Fourier imaging of hidden objects in thick turbid media," Optics Letters, Vol. 18, No. 3, pp. 241-243 (Feb. 1, 1993); Yoo et al., "Time-resolved coherent and incoherent components of forward light scattering in random media," Optics Letters, Vol. 15, No. 6, pp. 320-322 (Mar. 15, 1990); Chen et al., "Two-dimensional imaging through diffusing media using 150-fs gated electronic holography techniques," Optics Letters, Vol. 16, No. 7, pp. 487-489 (Apr. 1, 1991); Duncan et al., "Time-gated imaging through scattering media using stimulated Raman amplification," Optics Letters, Vol. 16, No. 23, pp. 1868-1870 (Dec. 1, 1991), all of which are incorporated herein by reference.
Of the above-listed art, Wang et al., "Kerr-Fourier imaging of hidden objects in thick turbid media," Optics Letters, Vol. 18, No. 3, pp. 241-243 (Feb. 1, 1993) is illustrative. In this article, there is disclosed a time/space-gating system for use in imaging opaque test bars hidden inside a 5.5 cm-thick 2.5% Intralipid solution. The disclosed system includes three main parts: a laser source, an optical Kerr gate and a detector. The laser source is a picosecond mode-locked laser system, which emits a 1054 nm, 8 ps laser pulse train as the illumination source. The second harmonic of the pulse train, which is generated by transmission through a potassium dihydrate phosphate (KDP) crystal, is used as the gating source. The illumination source is sent through a variable time-delay and is then used to transilluminate, from one side, the turbid medium containing the opaque object. The signal from the turbid medium located at the front focal plane of a lens is collected and transformed to a Kerr cell located at its back focal plane (i.e., the Fourier-transform spectral plane of a 4F system). That portion of the Kerr cell located at the focal point of the 4F system is gated at the appropriate time using the gating source so that only the ballistic and snake components are permitted to pass therethrough. The spatial-filtered and temporal-segmented signal is then imaged by a second lens onto a CCD camera.
Another technique for preferentially detecting ballistic and snake photons, as opposed to diffusive photons, for use in transillumination is described in co-pending U.S. patent application Ser. No. 08/573,939, filed Dec. 18, 1995, in the names of Robert R. Alfano et al, the disclosure of which is incorporated herein by reference. More specifically, the aforementioned application discloses a method and apparatus for imaging and/or characterizing a tissue based upon the extent to which initially polarized light maintains its polarization after propagating through the tissue. Said method and apparatus are based in part on the discovery that, when initially polarized light is transmitted through a turbid medium, such as human tissue, the ballistic and snake-like components of the light emergent from the turbid medium maintain the polarization of the initially polarized light while the diffuse component of the light emergent from the turbid medium becomes completely depolarized. In a preferred embodiment, said application teaches a method for imaging an object located in or behind a turbid medium which comprises the steps of (a) illuminating the object through the turbid medium with a pulse of light, the pulse of light being polarized and having an initial state of polarization, whereby light consisting of a ballistic component, a snake-like component and a diffuse component emerges from the illuminated turbid medium; (b) passing the emergent light from the illuminated turbid medium through a polarizing means which is alternately oriented parallel to the initial state of polarization of the pulse of light and perpendicular to the initial state of polarization of the pulse of light so as to enable the measurement of the parallel and perpendicular polarization components of the emergent light; (c) detecting the parallel and perpendicular polarization components of the emergent light; (d) subtracting the perpendicular polarization component from the parallel polarization component to yield a difference; and (e) forming an image of the object using said difference.
Still another technique for improving the quality of a transillumination image of an object hidden in a turbid medium is described in Yoo et al., "Imaging objects hidden in scattering media using a fluorescence-absorption technique," Optics Letters, 16(16):1252-4 (Aug. 15, 1991), which is incorporated herein by reference. More specifically, the aforementioned publication discloses a transillumination imaging technique wherein an object hidden in a scattering medium is made luminescent by the addition thereto of a contrast agent, and luminescent light emitted from the contrast agent is selected for imaging while the illuminating light is filtered out. The technique is based in part on the observation that, as illuminating light traverses through a highly scattering medium, its signal intensity (containing the image information) decreases whereas its multiply scattered light intensity (containing noise) decreases. The technique is further based in part on the observation that one way to reduce the amount of noise from the multiply scattered light is to shorten the distance the signal light traverses in the turbid medium. In accordance with said technique, such a shortening of the distance traversed by the light signal is achieved by making the object luminescent and then viewing the luminescent light. The quality of the image can be further improved by introducing an absorbing dye into the turbid medium that preferentially absorbs the luminescent light from the contrast agent. In this manner, because the multiply scattered light travels over a longer path length than the ballistic signal, the multiply scattered light is attenuated more than the signal light by absorption.
In addition to being used in the aforementioned manner, contrast agents have also been used in connection with a variety of different medical imaging techniques (e.g., X-ray, PGT, and CAT tomography) to enhance image quality and to increase the quantity of information obtained. The polarization properties of fluorescent light emitted by several contrast agents, such as Eosin, Rose Begal and TCTIF in non-turbid media, have been studied using picosecond time-dependent fluorescence measurements. See Fleming et al., "Direct observation of rotational diffusion by picosecond spectroscopy," Chem. Phys., 17:91-100 (1976) and Porter et al., "Picosecond rotational diffusion in kinetic and steady state fluorescence spectroscopy," Chem. Phys. Lett., 49:416-20 (1977), both of which are incorporated herein by reference. The results of such studies show that the aforementioned contrast agents, when photoexcited by polarized light, emit partially polarized light, keeping the preferred polarization of the pump light.
Accordingly, in view of the above, it can readily be appreciated that there is an outstanding need for a high resolution subsurface imaging technique adapted for use with turbid media. Imaging techniques employing optical coherence tomography (Huang et al., "Optical coherence tomography," Science, 254:1178-81 (1991)), confocal microscopy (Masters et al., "Ultraviolet confocal fluorescence microscopy of the in vitro cornea: redox metabolic imaging," Appl. Opt., 32:592-6 (1993)) and two-photon excitation microscopy (Denk et al., "Two-photon laser scanning fluorescence microscopy," Science, 248:73-6 (1990)) have been developed and do provide high resolution subsurface images; however, such techniques are limited by the fact that the imaging depth is small, i.e., on the order of about 1 mm or less.